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2.
Otol Neurotol ; 45(3): e193-e197, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38361299

RESUMO

OBJECTIVE: To validate how an automated model for vestibular schwannoma (VS) segmentation developed on an external homogeneous dataset performs when applied to internal heterogeneous data. PATIENTS: The external dataset comprised 242 patients with previously untreated, sporadic unilateral VS undergoing Gamma Knife radiosurgery, with homogeneous magnetic resonance imaging (MRI) scans. The internal dataset comprised 10 patients from our institution, with heterogeneous MRI scans. INTERVENTIONS: An automated VS segmentation model was developed on the external dataset. The model was tested on the internal dataset. MAIN OUTCOME MEASURE: Dice score, which measures agreement between ground truth and predicted segmentations. RESULTS: When applied to the internal patient scans, the automated model achieved a mean Dice score of 61% across all 10 images. There were three tumors that were not detected. These tumors were 0.01 ml on average (SD = 0.00 ml). The mean Dice score for the seven tumors that were detected was 87% (SD = 14%). There was one outlier with Dice of 55%-on further review of this scan, it was discovered that hyperintense petrous bone had been included in the tumor segmentation. CONCLUSIONS: We show that an automated segmentation model developed using a restrictive set of siloed institutional data can be successfully adapted for data from different imaging systems and patient populations. This is an important step toward the validation of automated VS segmentation. However, there are significant shortcomings that likely reflect limitations of the data used to train the model. Further validation is needed to make automated segmentation for VS generalizable.


Assuntos
Neuroma Acústico , Humanos , Neuroma Acústico/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos
3.
Clin Trials ; 21(1): 18-28, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38321701

RESUMO

BACKGROUND: Neurofibromatosis type 2-related schwannomatosis is a genetic disease characterized by the development of bilateral vestibular schwannomas, ependymomas, meningiomas, and cataracts. Mild to profound hearing loss and tinnitus are common symptoms reported by individuals with neurofibromatosis type 2. While tinnitus is known to have a significant and negative impact on the quality of life of individuals from the general population, the impact on individuals with neurofibromatosis type 2 is unknown. Consensus regarding the selection of suitable patient-reported outcome measures for assessment could advance further research into tinnitus in neurofibromatosis type 2 patients. The purpose of this work is to achieve a consensus recommendation by the Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration for patient-reported outcome measures used to evaluate quality of life in the domain of tinnitus for neurofibromatosis type 2 clinical trials. METHODS: The Response Evaluation in Neurofibromatosis and Schwannomatosis Patient-Reported Outcomes Communication Subgroup systematically evaluated patient-reported outcome measures of quality of life in the domain of tinnitus for individuals with neurofibromatosis type 2 using previously published Response Evaluation in Neurofibromatosis and Schwannomatosis rating procedures. Of the 19 identified patient-reported outcome measures, 3 measures were excluded because they were not validated as an outcome measure or could not have been used as a single outcome measure for a clinical trial. Sixteen published patient-reported outcome measures for the domain of tinnitus were scored and compared on their participant characteristics, item content, psychometric properties, and feasibility for use in clinical trials. RESULTS: The Tinnitus Functional Index was identified as the most highly rated measure for the assessment of tinnitus in populations with neurofibromatosis type 2, due to strengths in the areas of item content, psychometric properties, feasibility, and available scores. DISCUSSION: Response Evaluation in Neurofibromatosis and Schwannomatosis currently recommends the Tinnitus Functional Index for the assessment of tinnitus in neurofibromatosis type 2 clinical trials.


Assuntos
Neurilemoma , Neurofibromatoses , Neurofibromatose 2 , Neoplasias Cutâneas , Zumbido , Humanos , Neurofibromatose 2/complicações , Neurofibromatose 2/diagnóstico , Neurofibromatose 2/genética , Zumbido/diagnóstico , Zumbido/etiologia , Qualidade de Vida , Neurofibromatoses/complicações , Neurofibromatoses/diagnóstico , Medidas de Resultados Relatados pelo Paciente
4.
Laryngoscope ; 134(6): 2879-2888, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38197496

RESUMO

OBJECTIVE(S): Recently directed methods of inner ear drug delivery underscore the necessity for understanding critical anatomical dimensions. This study examines anatomical measurements of the human middle and inner ear relevant for inner ear drug delivery studied with three different imaging modalities. METHODS: Post-mortem human temporal bones were analyzed using human temporal bone histopathology (N = 24), micro computerized tomography (µCT; N = 4), and synchrotron radiation phase-contrast imaging (SR-PCI; N = 7). Nine measurements involving the oval and round windows were performed when relevant anatomical structures were visualized for subsequent age-controlled analysis, and comparisons were made between imaging methods. RESULTS: Combined human temporal bone histopathology showed the mean distance to the saccule from the center of the stapes footplate (FP) was 2.07 ± 0.357 mm and the minimum distance was 1.23 mm. The mean distance from the round window membrane (RWM) to the osseous spiral lamina (OSL) was 1.75 ± 0.199 mm and the minimum distance was 1.43 mm. Instruments inserted up to 1 mm past the center of the FP are unlikely to cause saccular damage, provided there are no endolymphatic hydrops. Similarly, instruments inserted up to 1 mm through the RWM in the trajectory toward the OSL are unlikely to cause OSL damage. CONCLUSION: The combined analyses of inner-ear dimensions of age-controlled groups and imaging modalities demonstrate critical dimensions of importance to consider when inserting delivery vehicles into the human cochlea. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:2879-2888, 2024.


Assuntos
Orelha Interna , Terapia Genética , Osso Temporal , Microtomografia por Raio-X , Humanos , Osso Temporal/diagnóstico por imagem , Osso Temporal/anatomia & histologia , Orelha Interna/diagnóstico por imagem , Orelha Interna/anatomia & histologia , Microtomografia por Raio-X/métodos , Terapia Genética/métodos , Cadáver , Pessoa de Meia-Idade , Masculino , Feminino , Síncrotrons , Idoso
5.
Laryngoscope ; 134 Suppl 5: S1-S14, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37776249

RESUMO

OBJECTIVES: This study compared the immune-related secretory capacity of human vestibular schwannoma (VS) and tumor-assisted macrophages (TAMs) with their normal counterparts (Schwann cells [SC] and peripheral blood monocyte-derived macrophages [Mo-MFs], respectively), and examined relationships with presurgical hearing and tumor size. METHODS: VS tumors (n = 16), auditory nerve (n = 1), blood (n = 9), and great auricular nerves (n = 3) were used. SCs (S100B+ ) and TAMs (CD68+ ) were isolated from VS tissue for culture. The secreted levels of 65 immune-related factors were measured and compared using unpaired t-tests with Welch correction (schwannoma vs. SCs) or Mann-Whitney tests (TAMs and Mo-MFs). Associations between factor concentration and word recognition (WR), pure-tone average (PTA), and tumor size were evaluated with Spearman correlation. RESULTS: Secreted factors with significantly higher concentrations in schwannoma versus SC supernatants included IL-2 and BAFF, whereas MMP-1, IL-6, FGF-2, VEGF-A, MIP-3α, and GRO-α concentrations were significantly higher in TAMs versus Mo-MFs (all p < 0.05). Worse WR was significantly associated with higher secretion of fractalkine, eotaxin-3, CD30, and IL-16 by VS cells; IP-10, eotaxin-3, multiple interleukins, GM-CSF, SCF, and CD30 by TAMs; and TNF-α and MIP-1α by Mo-MFs (all p < 0.05). Worse PTA was significantly correlated with higher secretion of IL-16 by VS cells (p < 0.05). Larger tumor size was significantly correlated with higher secretion of eotaxin by VS cells, and of IL-7, IL-21, and LIF by TAMs (all p = 0.017). CONCLUSIONS: Differential secretion of immune-related factors was observed in schwannoma versus normal SCs and in TAMs versus Mo-MFs, some of which were correlated with worse hearing and larger VS tumors. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:S1-S14, 2024.


Assuntos
Neurilemoma , Neuroma Acústico , Humanos , Neuroma Acústico/patologia , Quimiocina CCL26 , Macrófagos Associados a Tumor/patologia , Interleucina-16
6.
Sci Adv ; 9(45): eadf7295, 2023 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-37948527

RESUMO

Vestibular schwannoma (VS) is an intracranial tumor arising from neoplastic Schwann cells and typically presenting with hearing loss. The traditional belief that hearing deficit is caused by physical expansion of the VS, compressing the auditory nerve, does not explain the common clinical finding that patients with small tumors can have profound hearing loss, suggesting that tumor-secreted factors could influence hearing ability in VS patients. We conducted profiling of patients' plasma for 66 immune-related factors in patients with sporadic VS (N > 170) and identified and validated candidate biomarkers associated with tumor size (S100B) and hearing (MCP-3). We further identified a nine-biomarker panel (TNR-R2, MIF, CD30, MCP-3, IL-2R, BLC, TWEAK, eotaxin, and S100B) with outstanding discriminatory ability for VS. These findings revealed possible therapeutic targets for VS, providing a unique diagnostic tool that may predict hearing change and tumor growth in VS patients, and may inform the timing of tumor resection to preserve hearing.


Assuntos
Surdez , Perda Auditiva , Neuroma Acústico , Humanos , Neuroma Acústico/diagnóstico , Neuroma Acústico/patologia , Neuroma Acústico/cirurgia , Perda Auditiva/etiologia , Audição , Biomarcadores
7.
Brain Commun ; 5(2): fcad089, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37025569

RESUMO

Neurofibromatosis type 2-related schwannomatosis is a genetic disorder characterized by neurologic tumours, most typically vestibular schwannomas that originate on the vestibulo-cochlear nerve(s). Although vestibular symptoms can be disabling, vestibular function has never been carefully analysed in neurofibromatosis type 2-related schwannomatosis. Furthermore, chemotherapy (e.g. bevacizumab) can reduce tumour volume and improve hearing in neurofibromatosis type 2-related schwannomatosis, but nothing is known about its vestibular effects. In this report, we studied the three primary vestibular-mediated behaviours (eye movements, motion perception and balance), clinical vestibular disability (dizziness and ataxia), and imaging and hearing in eight untreated patients with neurofibromatosis type 2-related schwannomatosis and compared their results with normal subjects and patients with sporadic, unilateral vestibular schwannoma tumours. We also examined how bevacizumab affected two patients with neurofibromatosis type 2-related schwannomatosis. Vestibular schwannomas in neurofibromatosis type 2-related schwannomatosis degraded vestibular precision (inverse of variability, reflecting a reduced central signal-to-noise ratio) but not vestibular accuracy (amplitude relative to ideal amplitude, reflecting the central signal magnitude) and caused clinical disability. Bevacizumab improved vestibular precision and clinical disability in both patients with neurofibromatosis type 2-related schwannomatosis but did not affect vestibular accuracy. These results demonstrate that vestibular schwannoma tumours in our neurofibromatosis type 2-related schwannomatosis population degrade the central vestibular signal-to-noise ratio, while bevacizumab improves the signal-to-noise ratio, changes that can be explained mechanistically by the addition (schwannoma) and suppression (bevacizumab) of afferent neural noise.

8.
Otolaryngol Clin North Am ; 56(3): 543-556, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37024334

RESUMO

Vestibular schwannomas continue to cause hearing loss, facial nerve paralysis, imbalance, and tinnitus. These symptoms are compounded by germline neurofibromatosis type 2 (NF2) gene loss and multiple intracranial and spinal cord tumors associated with NF2-related schwannomatosis. The current treatments of observation, microsurgical resection, or stereotactic radiation may prevent catastrophic brainstem compression but are all associated with the loss of cranial nerve function, particularly hearing loss. Novel targeted treatment options to stop tumor progression include small molecule inhibitors, immunotherapy, anti-inflammatory drugs, radio-sensitizing and sclerosing agents, and gene therapy.


Assuntos
Perda Auditiva , Neurilemoma , Neurofibromatoses , Neurofibromatose 2 , Neuroma Acústico , Neoplasias Cutâneas , Humanos , Neuroma Acústico/genética , Neuroma Acústico/terapia , Neurilemoma/patologia , Neurofibromatoses/diagnóstico , Neurofibromatoses/cirurgia , Neoplasias Cutâneas/cirurgia , Neurofibromatose 2/cirurgia
9.
Curr Oncol ; 30(3): 3473-3483, 2023 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-36975476

RESUMO

(1) Background: This study aimed to evaluate the efficacy and treatment-related toxicity of proton radiotherapy (PRT) for vestibular schwannoma (VS) in patients with neurofibromatosis type 2-related schwannomatosis (NF2). (2) Methods: Consecutive NF2 patients treated with PRT for VS between 2004 and 2016 were retrospectively evaluated, focusing on tumor volume, facial and trigeminal nerve function, hearing, tinnitus, vestibular symptoms, and the need for salvage therapy after PRT. (3) Results: Eight patients were included (median age 36 years, 50% female). Median follow-up was 71 months. Five (63%) patients received fractionated PRT and three (38%) received PRT radiosurgery for VS. Six patients (75%) received prior VS surgery; three also received bevacizumab. Six patients (75%) did not require salvage therapy after PRT. Two patients (25%) with residual hearing lost it after PRT, and six had already lost ipsilateral hearing prior to PRT. Tumor and treatment-related morbidity could be evaluated in six patients. Following PRT, conditions that occurred or worsened were: facial paresis in five (83%), trigeminal hypoesthesia in two (33%), tinnitus in two (33%), and vestibular symptoms in four patients (67%). (4) Conclusion: After PRT for VS, the majority of the NF2 patients in the cohort did not require additional therapy. Tumor and/or treatment-related cranial nerve deficits were common. This is at least partly explained by the use of PRT as a salvage treatment after surgery or bevacizumab, in the majority of cases. There remains the further opportunity to elucidate the efficacy and toxicity of proton radiotherapy as a primary treatment.


Assuntos
Neurofibromatose 2 , Neuroma Acústico , Zumbido , Humanos , Feminino , Adulto , Masculino , Neurofibromatose 2/complicações , Neurofibromatose 2/radioterapia , Neurofibromatose 2/diagnóstico , Neuroma Acústico/radioterapia , Neuroma Acústico/cirurgia , Prótons , Estudos Retrospectivos , Bevacizumab/uso terapêutico , Resultado do Tratamento , Seguimentos
10.
JAMA Otolaryngol Head Neck Surg ; 149(5): 404-415, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36928544

RESUMO

Importance: Persistent tinnitus is common, disabling, and difficult to treat. Objective: To evaluate the association between circulating metabolites and persistent tinnitus. Design, Setting, and Participants: This was a population-based case-control study of 6477 women who were participants in the Nurses' Health Study (NHS) and NHS II with metabolomic profiles and tinnitus data. Information on tinnitus onset and frequency was collected on biennial questionnaires (2009-2017). For cases, metabolomic profiles were measured (2015-2021) in blood samples collected after the date of the participant's first report of persistent tinnitus (NHS, 1989-1999 and 2010-2012; NHS II, 1996-1999). Data analyses were performed from January 24, 2022, to January 14, 2023. Exposures: In total, 466 plasma metabolites from 488 cases of persistent tinnitus and 5989 controls were profiled using 3 complementary liquid chromatography tandem mass spectrometry approaches. Main Outcomes and Measures: Logistic regression was used to estimate odds ratios (ORs) of persistent tinnitus (per 1 SD increase in metabolite values) and 95% CIs for each individual metabolite. Metabolite set enrichment analysis was used to identify metabolite classes enriched for associations with tinnitus. Results: Of the 6477 study participants (mean [SD] age, 52 [9] years; 6477 [100%] female; 6121 [95%] White individuals) who were registered nurses, 488 reported experiencing daily persistent (≥5 minutes) tinnitus. Compared with participants with no tinnitus (5989 controls), those with persistent tinnitus were slightly older (53.0 vs 51.8 years) and more likely to be postmenopausal, using oral postmenopausal hormone therapy, and have type 2 diabetes, hypertension, and/or hearing loss at baseline. Compared with controls, homocitrulline (OR, 1.32; (95% CI, 1.16-1.50); C38:6 phosphatidylethanolamine (PE; OR, 1.24; 95% CIs, 1.12-1.38), C52:6 triglyceride (TAG; OR, 1.22; 95% CIs, 1.10-1.36), C36:4 PE (OR, 1.22; 95% CIs, 1.10-1.35), C40:6 PE (OR, 1.22; 95% CIs, 1.09-1.35), and C56:7 TAG (OR, 1.21; 95% CIs, 1.09-1.34) were positively associated, whereas α-keto-ß-methylvalerate (OR, 0.68; 95% CIs, 0.56-0.82) and levulinate (OR, 0.60; 95% CIs, 0.46-0.79) were inversely associated with persistent tinnitus. Among metabolite classes, TAGs (normalized enrichment score [NES], 2.68), PEs (NES, 2.48), and diglycerides (NES, 1.65) were positively associated, whereas phosphatidylcholine plasmalogens (NES, -1.91), lysophosphatidylcholines (NES, -2.23), and cholesteryl esters (NES,-2.31) were inversely associated with persistent tinnitus. Conclusions and Relevance: This population-based case-control study of metabolomic profiles and tinnitus identified novel plasma metabolites and metabolite classes that were significantly associated with persistent tinnitus, suggesting that metabolomic studies may help improve understanding of tinnitus pathophysiology and identify therapeutic targets for this challenging disorder.


Assuntos
Diabetes Mellitus Tipo 2 , Perda Auditiva , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos de Casos e Controles , Inquéritos e Questionários , Biomarcadores
11.
bioRxiv ; 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36747696

RESUMO

Vestibular schwannoma (VS) is intracranial tumor arising from neoplastic Schwann cells, causing hearing loss in about 95% of patients. The traditional belief that hearing deficit is caused by physical expansion of the VS, compressing the auditory nerve, does not explain the common clinical finding that patients with small tumors can have profound hearing loss, suggesting that tumor-secreted factors could influence hearing ability in VS patients. Here, we conducted profiling of patients' plasma for 67 immune-related factors on a large cohort of VS patients (N>120) and identified candidate biomarkers associated with tumor growth (IL-16 and S100B) and hearing (MDC). We identified the 7-biomarker panel composed of MCP-3, BLC, S100B, FGF-2, MMP-14, eotaxin, and TWEAK that showed outstanding discriminatory ability for VS. These findings revealed possible therapeutic targets for VS-induced hearing loss and provided a unique diagnostic tool that may predict hearing change and tumor growth in VS patients and may help inform the ideal timing of tumor resection to preserve hearing.

12.
Otol Neurotol ; 44(2): 183-190, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36624600

RESUMO

OBJECTIVE: In vestibular schwannoma patients, a loss of signal intensity (SI) on T2-weighted magnetic resonance imaging (MRI) has been reported within the ipsilateral labyrinth. The purpose of this study was to quantitatively evaluate the occurrence and course of this intensity loss in relation to proton radiotherapy and its possible association with hearing loss. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Patients who received proton therapy for a vestibular schwannoma and underwent at least two high-resolution T2-weighted cisternographic sequence (constructive interference in steady state/fast imaging employing steady-state acquisition/DRIVE) MRIs and audiometry assessments. MAIN OUTCOME MEASURES: Relative T2 SIs from the vestibules and basal/apical cochlear turns of the labyrinth, bilaterally. RESULTS: Ninety-five MRI scans from 34 patients were included. The apical turn of the ipsilateral cochlea showed a lower mean cochlear SI than on the contralateral side (±3.5 versus 5.0). The mean relative cochlear SI did not significantly change after proton radiotherapy. The ipsilateral vestibule showed a higher SI than the cochlea. The relative mean cochlear SI was not directly correlated to (the degree of) hearing loss before or after proton radiotherapy, nor did it predict future hearing loss. CONCLUSION: The relative mean cochlear SI on cisternographic T2-MRI in vestibular schwannoma patients is diminished on the treated side, when compared with the ipsilateral vestibule and the contralateral cochlea/vestibule. The SI of the ipsilateral cochlea does not further decrease after proton radiotherapy and seems to be related to the tumor rather than the therapy. The diminished cochlear SI does not correlate with subsequent loss of hearing.


Assuntos
Surdez , Líquidos Labirínticos , Neuroma Acústico , Humanos , Neuroma Acústico/complicações , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/radioterapia , Prótons , Estudos Retrospectivos , Cóclea/diagnóstico por imagem , Imageamento por Ressonância Magnética
13.
JAMA Otolaryngol Head Neck Surg ; 148(10): 985-986, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35925579

RESUMO

This cross-sectional study evaluates demographic characteristics, surgical characteristics, and audiometric data associated with closure of the air-bone gap to less than 10 dB or 15 dB.


Assuntos
Otosclerose , Cirurgia do Estribo , Condução Óssea , Humanos , Otosclerose/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
14.
Mol Ther Methods Clin Dev ; 26: 169-180, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-35846573

RESUMO

Loss of function of the neurofibromatosis type 2 (NF2) tumor suppressor gene leads to the formation of schwannomas, meningiomas, and ependymomas, comprising ∼50% of all sporadic cases of primary nervous system tumors. NF2 syndrome is an autosomal dominant condition, with bi-allelic inactivation of germline and somatic alleles resulting in loss of function of the encoded protein merlin and activation of mammalian target of rapamycin (mTOR) pathway signaling in NF2-deficient cells. Here we describe a gene replacement approach through direct intratumoral injection of an adeno-associated virus vector expressing merlin in a novel human schwannoma model in nude mice. In culture, the introduction of an AAV1 vector encoding merlin into CRISPR-modified human NF2-null arachnoidal cells (ACs) or Schwann cells (SCs) was associated with decreased size and mTORC1 pathway activation consistent with restored merlin activity. In vivo, a single injection of AAV1-merlin directly into human NF2-null SC-derived tumors growing in the sciatic nerve of nude mice led to regression of tumors over a 10-week period, associated with a decrease in dividing cells and an increase in apoptosis, in comparison with vehicle. These studies establish that merlin re-expression via gene replacement in NF2-null schwannomas is sufficient to cause tumor regression, thereby potentially providing an effective treatment for NF2.

15.
J Neurophysiol ; 127(2): 596-606, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35080420

RESUMO

Imbalance and dizziness are disabling symptoms for many patients with vestibular schwannomas (VS) but symptom severity typically does not correlate with the vestibulo-ocular reflex (VOR) amplitude-based metrics used to assess peripheral vestibular damage. In this study, we tested the hypothesis that imbalance and dizziness in patients with VS relate to VOR metrics that are not based on response amplitude. Twenty-four patients with unilateral, sporadic VS tumors were studied, and objective (balance) and subjective (dizziness) vestibular dysfunction was quantified. The VOR was tested using two yaw-axis motion stimuli, low-frequency en-bloc sinusoidal, and high-frequency head-on-body impulsive rotations. Imbalance correlated with VOR precision (the inverse of the trial-to-trial variability) and with low-frequency VOR dynamics (quantified with the time constant), and these two metrics were also strongly correlated. Dizziness correlated with the VOR bias caused by an imbalance in static central vestibular tone, but not with dynamic VOR metrics. VOR accuracy (mean response amplitude relative to the ideal response) was not correlated with the severity of imbalance or dizziness or with measures of VOR precision or time constant. Imbalance in patients with VS, therefore, scales with VOR precision and time constant, both of which appear to reflect the central vestibular signal-to-noise ratio, but not with VOR slow-phase accuracy, which is based on the magnitude of the central vestibular signals. Dizziness was related to the presence of a static central tone imbalance but not to any VOR metrics, suggesting that abnormal perception in VS may be affected by factors that are not captured by yaw-axis VOR measurements.NEW & NOTEWORTHY The severity of symptoms associated with unilateral vestibular schwannomas (VS) is poorly correlated with standard yaw-axis vestibulo-ocular reflex (VOR) metrics that are based on response amplitude. In this study, we show that the balance and perceptual dysfunction experienced by patients with VS scales with VOR metrics that capture information about the central signal-to-noise ratio (balance) and central static tone (dizziness), but are not correlated with the VOR gain, which reflects central signal amplitude.


Assuntos
Tontura/fisiopatologia , Neuroma Acústico/fisiopatologia , Equilíbrio Postural/fisiologia , Reflexo Vestíbulo-Ocular/fisiologia , Adulto , Tontura/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroma Acústico/complicações
16.
Ann Otol Rhinol Laryngol ; 131(6): 683-689, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34353140

RESUMO

OBJECTIVE: To describe the presentation and treatment of patients developing pulmonary embolism following translabyrinthine approach for vestibular schwannoma resection. METHODS: This was a retrospective case series of patients at 2 academic tertiary medical centers who developed symptomatic pulmonary embolism post-operatively following translabyrinthine approach for vestibular schwannoma resection and were found to have evidence of sigmoid sinus thrombosis. RESULTS: Three patients were identified to have post-operative pulmonary emboli after translabyrinthine approach for vestibular schwannoma resection with sigmoid sinus or internal jugular vein clots in the absence of lower extremity deep vein thrombosis. Caprini scores for these patients were 5 or lower. All patients underwent CT pulmonary angiography and were confirmed to have pulmonary emboli. Two were promptly anticoagulated with heparin drips and transitioned to long-term oral anticoagulation therapy and 1 had delayed anticoagulation. None of these patients suffered from intracranial hemorrhage post-operatively. CONCLUSIONS: Patients undergoing translabyrinthine approach for vestibular schwannoma can develop pulmonary embolism from sigmoid sinus entry or thrombosis. No clear guidelines exist for the management of this complication in the setting of recent craniotomy and the risk of intracranial hemorrhage must be considered prior to initiating anticoagulation.


Assuntos
Neuroma Acústico , Embolia Pulmonar , Trombose dos Seios Intracranianos , Trombose Venosa , Anticoagulantes/uso terapêutico , Humanos , Hemorragias Intracranianas/complicações , Neuroma Acústico/complicações , Neuroma Acústico/cirurgia , Embolia Pulmonar/complicações , Estudos Retrospectivos , Trombose dos Seios Intracranianos/complicações , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologia
17.
Laryngoscope Investig Otolaryngol ; 6(5): 1008-1019, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34667843

RESUMO

OBJECTIVES: Two pilot studies of AR-42, a pan-histone deacetylase inhibitor, in human neurofibromatosis type 2 (NF2), vestibular schwannomas (VS), and meningiomas are presented. Primary endpoints included safety, and intra-tumoral pharmacokinetics (PK) and pharmacodynamics (PD). METHODS: Pilot 1 is a subset analysis of a phase 1 study of AR-42 in solid tumors, which included NF2 or sporadic meningiomas. Tumor volumes and treatment-related adverse events (TRAEs) are reported (NCT01129193).Pilot 2 is a phase 0 surgical study of AR-42 assessing intra-tumoral PK and PD. AR-42 was administered for 3 weeks pre-operatively. Plasma and tumor drug concentrations and p-AKT expression were measured (NCT02282917). RESULTS: Pilot 1: Five patients with NF2 and two with sporadic meningiomas experienced a similar incidence of TRAEs to the overall phase I trial. The six evaluable patients had 15 tumors (8 VS, 7 meningiomas). On AR-42, tumor volume increased in six, remained stable in eight, and decreased in one tumor. The annual percent growth rate decreased in eight, remained stable in three, and increased in four tumors. Pilot 2: Four patients with sporadic VS and one patient with meningioma experienced no grade 3/4 toxicities. Expression of p-AKT decreased in three of four VS. All tumors had higher AR-42 concentrations than plasma. CONCLUSIONS: AR-42 is safe. Tumor volumes showed a mixed response, but most slowed growth. On a 40-mg regimen, drug concentrated in tumors and growth pathways were suppressed in most tumors, suggesting this may be a well-tolerated and effective dose. A phase 2 study of AR-42 for NF2-associated tumors appears warranted. LEVEL OF EVIDENCE: 1b, 4.

18.
Front Oncol ; 11: 698192, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604034

RESUMO

The neurofibromatosis syndromes, including NF1, NF2, and schwannomatosis, are tumor suppressor syndromes characterized by multiple nervous system tumors, particularly Schwann cell neoplasms. NF-related tumors are mainly treated by surgery, and some of them have been treated by but are refractory to conventional chemotherapy. Recent advances in molecular genetics and genomics alongside the development of multiple animal models have provided a better understanding of NF tumor biology and facilitated target identification and therapeutic evaluation. Many targeted therapies have been evaluated in preclinical models and patients with limited success. One major advance is the FDA approval of the MEK inhibitor selumetinib for the treatment of NF1-associated plexiform neurofibroma. Due to their anti-neoplastic, antioxidant, and anti-inflammatory properties, selected natural compounds could be useful as a primary therapy or as an adjuvant therapy prior to or following surgery and/or radiation for patients with tumor predisposition syndromes, as patients often take them as dietary supplements and for health enhancement purposes. Here we review the natural compounds that have been evaluated in NF models. Some have demonstrated potent anti-tumor effects and may become viable treatments in the future.

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